Selective Targeting of Pancreatic Cancer SPORE

STop癌孢子摘要 胰腺癌仍然是一种致命的疾病，治疗选择有限。选择增加了， 在过去的5年里，我们进行了大量的基因组分析和临床前研究。然而，尽管取得了进展， 胰腺癌仍然是一种致命的疾病，五年生存率为10%，预计胰腺癌的死亡率为 到2030年将超过乳腺癌、前列腺癌和结直肠癌的死亡人数，成为全球第二大癌症死亡原因。 癌症死亡发病率迅速上升，自2010年以来增加了23%，自2012年以来增加了57%。 2006.病因学和最近上升的原因仍然知之甚少，与复杂的相互作用的躯体 在人口老龄化背景下的遗传、基因组、表观遗传和环境因素。 与许多实体瘤不同，单独的突变不足以产生治愈性靶向治疗， 临床上有用的生物标志物或共有亚型。仍然存在的挑战包括： ·低肿瘤细胞性阻碍了遗传和基因组研究，包括无法识别 生物标志物/亚型，以定制治疗 ·化疗和靶向治疗抗性肿瘤细胞群 ·促结缔组织增生基质，其可以是肿瘤促进和治疗抑制两者 ·由于抑制性骨髓细胞和T效应细胞缺乏而导致的免疫抑制环境 ·精确的肿瘤学方法仍然有限 ·临床试验每次仅限于1-2种疗法 我们已经组织了三个项目来直接解决这些问题;每个项目都有一个嵌入式的早期阶段 临床试验，将产生患者样本，以测试我们的SPORE的假设。蓬勃发展 研究和职业提升计划包括基于高度成功的模式在斯坦福大学 莱恩伯格这些将得到大量机构承诺的支持。一位非常有成就 一个多学科的调查小组与几个机构合作， 其中包括那些做出创新和高影响力贡献、提供临床服务的人 护理并进行了与胰腺癌密切相关的临床和转化研究。认识到需要 胰腺癌快速转化为临床，我们的组织采购，病理学和基因组学 核心和综合定量科学核心与项目无缝合作，以处理和分析 数据我们的SToP Cancer SPORE目标是为临床试验设计建立一个新的范例， 单一疗法或生物标志物。

SToP CANCER SPORE ABSTRACT Pancreatic cancer remains a lethal disease with limited therapeutic options. Options have increased over the last 5 years, with large genomic analyses and preclinical efforts. However, despite advances, pancreatic cancer remains a lethal disease with a five-year survival rate of 10%, and deaths from pancreatic cancer are expected to surpass deaths from breast, prostate and colorectal cancer by 2030, to become the second leading cause of cancer deaths. The incidence is rapidly increasing, with, a 23% increase since 2010 and 57% increase since 2006. The etiology and reason for the recent rise remain poorly understood with a complex interplay of somatic genetic, genomic, epigenetic and environmental factors in the context of an aging population. Unlike many solid tumors, mutations alone have not been sufficient to yield curative targeted therapies, clinically useful biomarkers or consensus subtypes. Challenges that remain include: · Low tumor cellularity hampers both genetic and genomic studies, including the inability to identify biomarkers/subtypes to tailor therapies · Chemotherapy and targeted therapy resistant tumor cell populations · Desmoplastic stroma that may be both tumor promoting and therapy inhibiting · Immunosuppressive environment due to suppressive myeloid cells and a paucity of T effector cells · Precision oncology approaches are still limited · Clinical trials are limited to only 1-2 therapies at a time We have assembled three projects that directly address these issues; each has an embedded early phase clinical trial that will yield patient samples with which to test our SPORE’s hypotheses. Robust Development Research and Career Enhancement Programs are included based on the highly successful models at UNC Lineberger. These will be backed by a substantial institutional commitment. A highly accomplished multidisciplinary team of investigators with collaborations across several institutions have been brought together that includes those who have made innovative and high impact contributions, delivered clinical care and performed clinical and translational research germane to pancreatic cancer. Recognizing the need for pancreatic cancer rapid translation to the clinic, our Tissue Procurement, Pathology, and Genomics Core and Integrative Quantitative Sciences Core work seamlessly with the projects to process and analyze data. Our SToP Cancer SPORE goal is to establish a new paradigm for clinical trial design that is not limited to a single therapy or biomarker.